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In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. Increased circulating sST2 level is associated with more severe pathological changes in female individuals with AD. These findings demonstrate how sST2 level is modulated by a genetic variation and plays a disease-causing role in females with AD. AD is the most common neurodegenerative disease and a leading cause of mortality in older people 1.

This suggests that microglial dysfunction plays an essential causative role in AD. Moreover, the soluble form of a full-length VCAM1 protein in endothelial cells, sVCAM1, is increased in the plasma and CSF of individuals with AD 17 , 18 ; this is suggested to mediate reduced hippocampal neurogenesis and a pro-inflammatory response by microglia during aging Other secreted proteins that contribute to AD pathogenesis include soluble cytokine receptors comprising the ectodomains of membrane-bound cytokine receptors, which function as decoy receptors to attenuate cytokine-mediated signaling 20 , Altered sST2 level in plasma is a biomarker of several inflammatory and cardiac diseases 28 , 29 , 30 , Notably, recent evidence shows that sST2 levels are also elevated in the blood of individuals with mild cognitive impairment MCI or AD 24 , Nonetheless, it is unclear what regulatory mechanisms underlie sST2 dysregulation and whether sST2 plays a pathological role in AD.

In the present study, we investigated sST2 regulation in AD and its roles in disease pathogenesis. We showed that sST2 level increases in the blood and brains of females with AD and is positively associated with disease progression. We then performed a linear regression analysis between plasma sST2 level and AD and its related endophenotypes, adjusting for age, sex, status of cardiovascular diseases CVDs; that is, heart disease, hypertension, diabetes mellitus and hyperlipidemia , body mass index BMI and education level, followed by multiple testing correction.